Injectable rhBMP‐2‐loaded chitosan hydrogel composite: Osteoinduction at ectopic site and in segmental long bone defect

Carriers for bone morphogenetic protein‐2 (BMP‐2) used in clinical practice still suffer from limitations such as insufficient protein retention. In addition, there is a clinical need for injectable carriers. The main objective of this study was to assess bone forming ability of rhBMP‐2 combined either with chitosan hydrogel (rhBMP‐2/CH) or chitosan hydrogel containing β‐tricalcium phosphate (β‐TCP) (rhBMP‐2/CH/TCP). Formulations were first compared in a rat ectopic intramuscular bone formation model, and the optimal formulation was further evaluated in healing of 15‐mm critical size defect in the radius of a rabbit. Three weeks after injection ectopically formed bone was analyzed by microcomputerized tomography (micro‐CT) and histology. Significantly higher (4.7‐fold) mineralized bone formation was observed in the rhBMP‐2/CH/TCP group compared to rhBMP‐2/CH group. In a pilot study, defect in a rabbit radius treated with rhBMP‐2/CH/TCP showed incomplete regeneration at 8 weeks with composite leakage from the defect, indicating the need for formulation refinement when segmental defect repair is foreseen. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010.